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Biomedical subjects

G Davies

Publications and source records attributed to G Davies.

At least 145 records · Page 8Linked to original sources
PubMed1996

Pharmacokinetics of opioids in renal dysfunction.

Patients with renal insufficiency commonly require the administration of an opioid analgesic to provide adequate pain relief. The handling of morphine, pethidine (meperidine) and dextropropoxyphene in patients with renal insufficiency is complicated by the potential accumulation of metabolites. While morphine itself remains largely unaffected by renal failure, accumulation, as denoted by an increase in both mean peak concentrations and the area under the concentration-time curve, of both the active metabolite (morphine-6-glucuronide) and the principal metabolite (morphine-3-glucuronide, thought to possess opiate antagonist properties) have been reported. The increased elimination half-lives of the toxic metabolites norpethidine and norpropoxyphene in patients with poor renal function administered pethidine and dextropropoxyphene, respectively, makes their routine use ill advised. Case reports of prolonged narcosis associated with the use of both codeine and dihydrocodeine in patients with renal insufficiency call for care to be used when prescribing these agents under such conditions. Although the pharmacokinetics of buprenorphine, alfentanil, sufentanil and remifentanil change little in patients with renal failure, the continuous administration of fentanyl can lead to prolonged sedation.

Analgesics, Opioid↗
PubMed1996

The vocational training scheme: decision-making in relation to general dental practitioners participating as scheme trainers.

In recent years, well-documented changes have occurred in the patterns of oral disease and, as a result, the scope and complexity of dental treatments has widened considerably. In response to this the Department of Health has introduced a compulsory one-year postgraduate vocational training scheme [VTS]. In this scheme, new graduates spend time in approved general dental practices, trained by selected general dental practitioners [GDPs] who are seen as having 'best practice' standards. For the VTS to succeed it will require the continued support of these 'best quality' GDPs who at the moment are competing for places as trainers. Such competition has not always existed and this paper describes a decision-making model for trainers which was developed because future external influences could reverse this competitive scenario, with a major effect on the postgraduate training programme.

Decision Making↗
PubMed1995

Structures and mechanisms of glycosyl hydrolases.

The wealth of information provided by the recent structure determinations of many different glycosyl hydrolases shows that the substrate specificity and the mode of action of these enzymes are governed by exquisite details of their three-dimensional structures rather than by their global fold.

Binding Sites↗
PubMed1995

Conserved catalytic machinery and the prediction of a common fold for several families of glycosyl hydrolases.

The regions surrounding the catalytic amino acids previously identified in a few "retaining" O-glycosyl hydrolases (EC 3.2.1) have been analyzed by hydrophobic cluster analysis and have been used to define sequence motifs. These motifs have been found in more than 150 glycosyl hydrolase sequences representing at least eight established protein families that act on a large variety of substrates. This allows the localization and the precise role of the catalytic residues (nucleophile and acid catalyst) to be predicted for each of these enzymes, including several lysosomal glycosidases. An identical arrangement of the catalytic nucleophile was also found for S-glycosyl hydrolases (myrosinases; EC 3.2.3.1) for which the acid catalyst is lacking. A (beta/alpha)8 barrel structure has been reported for two of the eight families of proteins that have been grouped. It is suggested that the six other families also share this fold at their catalytic domain. These enzymes illustrate how evolutionary events led to a wide diversification of substrate specificity with a similar disposition of identical catalytic residues onto the same ancestral (beta/alpha)8 barrel structure.

Amino Acid Sequence↗
PubMed1995

Familial Hypercholesterolaemia Regression Study: a randomised trial of low-density-lipoprotein apheresis.

Low-density-lipoprotein (LDL) apheresis has the theoretical advantage over anion-exchange resins and hydroxymethylglutaryl coenzyme A inhibitors of decreasing lipoprotein(a) as well as LDL. To confirm this advantage, patients with heterozygous familial hypercholesterolaemia and coronary artery disease were randomised to receive LDL apheresis fortnightly (with disposable dextran sulphate/cellulose columns) plus simvastatin 40 mg daily, or colestipol 20 g plus simvastatin 40 mg daily. Quantitative coronary angiography was repeated after a mean of 2.1 years in 20 patients undergoing apheresis and in 19 on combination drug therapy. Changes in serum lipoproteins were similar in both groups apart from greater lowering by apheresis of LDL cholesterol (3.2 vs 3.4 mmol/L in drug group, p = 0.03) and lipoprotein(a) (geometric means 14 vs 21 mg/dL, p = 0.03). There were no significant differences in primary angiographic endpoints per patient but lesion-based and segment-based secondary endpoints were biased in favour of the drug group (change in minimum lumen diameter of lesions 0.07 vs -0.004 mm, p = 0.046; change in mean lumen diameter of segments 0.02 vs -0.06 mm, p = 0.01). None of the angiographic changes correlated with lipoprotein(a) concentrations. Per patient changes in % diameter stenosis and minimum lumen diameter in the two groups were as or more favourable than those observed in five published trials that assessed lipid-lowering drug therapy by quantitative coronary angiography. Although LDL apheresis combined with simvastatin was more effective than colestipol plus simvastatin in reducing LDL cholesterol and lipoprotein(a), it was less beneficial in influencing coronary atherosclerosis and should be reserved for patients unresponsive to drugs. Decreasing lipoprotein(a) seems to be unnecessary if LDL cholesterol is reduced to 3.4 mmol/L or less.

Adult↗
PubMed1995

Purification, crystallisation and preliminary X-ray analysis of the vanadium-dependent haloperoxidase from Corallina officinalis.

The vanadium-dependent haloperoxidase from the seaweed Corallina officinalis has been purified to homogeneity and crystallised. The protein is reported to be a hexamer of 12 x 64,000 Da, contains no haem, and is dependent on vanadium for activity. The crystals are grown from polyethylene glycol (PEG) 6,000 and 0.4 M potassium chloride. They are stable and diffract to better than 2 A resolution. They are of a cubic space group I23 (or 12(1)3) with cell dimensions a = b = c = 310 A.

Crystallization↗
PubMed1995

Are routine alpha-fetoprotein and acetylcholinesterase determinations still necessary at second-trimester amniocentesis? Impact of high-resolution ultrasonography.

OBJECTIVE: To audit routine measurement of alpha-fetoprotein (AFP) and acetylcholinesterase in amniotic fluid (AF) samples obtained at second-trimester amniocentesis. METHODS: We reviewed retrospectively 1737 consecutive AF specimens obtained for cytogenetic evaluation over a 4-year period and routinely assayed for AFP and acetylcholinesterase. In all instances, high-resolution ultrasonography was performed before amniocentesis. Details of pregnancy outcome of all cases with AF AFP levels greater than 2.0 multiples of the median and a positive or faint acetylcholinesterase band were obtained. RESULTS: There were 31 abnormal results (1.8%, 1 of 56). Of these, 25 cases had elevated AF AFP and/or positive acetylcholinesterase. Ultrasonography correctly identified all 18 fetuses with anomalies associated with abnormal levels of these biochemical markers, including open neural tube defects and/or anterior abdominal wall defects (17 cases) and fetal hydrops (one). In the remaining seven, no fetal anomalies were detected, and all neonates were structurally normal after birth. In addition, six pregnancies with faint acetylcholinesterase and normal AF AFP showed no fetal abnormalities at ultrasonographic examination and post-delivery. CONCLUSIONS: High-resolution ultrasonography was more accurate than AF biochemistry in the detection of congenital anomalies associated with elevated AFP levels and acetylcholinesterase in the AF. Routine measurement of these biochemical markers in AF samples obtained for cytogenetic analysis appears to have a very low yield and would therefore not be cost-effective in practices where high-resolution ultrasonography is performed before amniocentesis.

Acetylcholinesterase↗
PubMed1995

Determination of radiation-induced damage in lymphocytes using the micronucleus and microgel electrophoresis 'Comet' assays.

DNA damage assays may be useful as rapid predictors of normal tissue radiosensitivity in clinical samples. We measured in vitro radiation-induced (2 Gy) damage to lymphocytes from cancer patients and normal healthy donors using both the micronucleus and microgel electrophoresis (Comet) assays simultaneously. For damage assessment, there was a good correlation (P < 0.001) between the mean comet lengths and the fraction of cells with comets. There was no correlation with initial damage, determined as the proportion of cells within a sample that formed comets, in comparison with the mean frequency of micronuclei per binucleate cell. However, there appeared to be an association between the determination of repair proficiency in the Comet assay and the mean frequency of micronuclei per binucleate cell in lymphocytes from cancer patients.

DNA↗
PubMed1995

Variation in radiosensitivity due to cell age and split-dose recovery in polykaryons induced by cytochalasin.

We have investigated the properties of an in vitro cell survival assay that uses as its endpoint the ability to form polyploid cells (polykaryons) in the presence of cytochalasin B (CB). The criterion for survival is that a polykaryon-forming unit (PFU) must reach the arbitrary DNA content of at least 16C. The age-dependence of PFU sensitivity to 137Cs irradiation was determined using V79-379A cells synchronized at mitosis. Cells assayed as PFUs demonstrated much less variation in radiosensitivity with age than did clonogens, but the changes in curve shape were qualitatively similar. In both assays mitotic cells yielded an exponential survival curve while that obtained at 5 h (mid-late S) had a marked quadratic component. Owing to the small overall variation in PFU survival with age, at doses greater than about 25 Gy the surviving fraction at 5 h was lower than in mitosis. In both V79-379A and HeLa S3 cells, PFUs demonstrated a capacity for split-dose recovery and yielded recovery ratios at 2.6 at 50 Gy in V79 and 1.5 at 20 Gy in HeLa. Since these ratios were much lower than in clonogens at the same dose, we suggest that this is consistent with an association that we have previously demonstrated between PFU response and the clonogenic initial slope. In an attempt to clarify the DNA lesions to which PFUs may be sensitive, we determined PFU response following exposure to 254-nm UV irradiation. In contrast with ionizing radiation, PFU response to UV was very similar to that of clonogens. This suggests that following UV exposure the absence of cytokinesis in polykaryons may confer less protection than in the case of ionizing radiation, possibly due to fundamental differences in the spectrum of DNA lesions produced.

Animals↗
PubMed1995

Simple thoracostomy avoids chest drain insertion in prehospital trauma.

Tension pneumothorax and hemothorax are life-threatening emergencies that require immediate treatment. Field stabilization of trauma patients often requires rapid surgical drainage of these injuries but inevitably delays departure for hospital. Conventional treatment involves the insertion of a chest drain but we describe a modified technique of simple thoracostomy that is faster and simpler to perform and avoids the risks associated with insertion of the chest drain. Following use of a simple thoracostomy as an alternative to chest drain insertion in 45 patients at the roadside, this technique appears to have important advantages over conventional techniques and warrants further clinical evaluation.

Adolescent↗
PubMed1995

The genotypic relationship of Candida albicans strains isolated from the oral cavity of patients with denture stomatitis.

Fifty-seven isolates of Candida albicans were obtained from different sites within the oral cavities of 18 dental patients without AIDS or any malignancies. Eleven of the patients had oral candidosis associated with the wearing of dentures. The genotypic relationships of the individual isolates were determined by hybridisation of a C. albicans-specific moderately repetitive sequence, 27A, to EcoRI-digested C. albicans chromosomal DNA. From the DNA profiles, the isolates could be divided into 22 distinct genetic groups. In the majority of patients, a single unique strain of C. albicans appeared to dominate in the oral cavity. Re-infection following antifungal therapy was generally due to the re-emergence of the original infecting strain. The C. albicans strains isolated from dental plates did not form a distinct genetic group. These results suggest that denture stomatitis is due to the outgrowth of commensal strains of C. albicans.

Blotting, Southern↗
PubMed1995

Effect of diadenosine phosphates on human umbilical vessels: novel platelet-derived vasoconstrictors.

The responses of human isolated umbilical artery to the novel platelet-derived mediators, diadenosine phosphates, P1,P5-di(adenosine-5')pentaphosphate (AP5A) and P1,P6-di(adenosine-5')hexaphosphate (AP6A) were studied in vitro. AP5A (1 nM-300 microM; n = 7) and AP6A (1 nM-30 microM; n = 5) produced transient concentration-dependent contractions. Responses to AP5A were unaffected by co-incubation with indomethacin (10 microM; n = 4), NGmonomethyl-L-arginine (L-NMMA; 300 microM; n = 4) and theophylline (1 microM; n = 5). These results demonstrate that diadenosine phosphates have constrictor effects on human blood vessels in vitro and are consistent with a role for these platelet-derived mediators in the regulation of blood vessel tone.

Arginine↗
PubMed1995

Early remodelling of coronary stenoses after thrombolytic treatment in patients with acute myocardial infarction.

OBJECTIVE: To assess the frequency of early remodelling of coronary stenosis morphology after thrombolytic treatment in patients with acute myocardial infarction. DESIGN: Coronary angiograms were analysed by a computerised edge detection analysis system. Coronary stenosis severity was measured and morphology classified as smooth or complex. PATIENTS: Coronary arteriograms were obtained approximately 90 min and 24 h after thrombolytic treatment from 40 patients with acute myocardial infarction. MAIN RESULTS: Stenosis morphology was complex in 22 patients (65%) and smooth in 11 (32%) 90 min after thrombolysis. The morphology of 11 (50%) complex coronary stenoses and three (27%) smooth stenoses had changed at 24 h (P < 0.05). The transition from complex to smooth was associated with a reduction in stenosis severity from 65 (4)% to 51 (5)% (P < 0.05). The stenosis severity was 63 (4)% and 60 (5)% in those with persistently complex morphology, and 56 (7)% and 50 (5)% in those with persistently smooth morphology at 90 min and 24 h respectively (NS). CONCLUSIONS: Transition of morphology from complex to smooth within 24 h is common. This transition is associated with a reduction in stenosis severity of a degree greater than that found in persistently smooth stenoses over the same interval. 50% of stenoses are smooth at 24 h.

Adult↗
PubMed1994

Effect of non-attenders on the potential of a primary care programme to reduce cardiovascular risk in the population. Family Heart Study Group.

OBJECTIVES: To determine the feasibility of enrolling non-attenders of a population based cardiovascular risk reduction programme (the British family heart study) into a further, similar programme and to assess the effect of non-attendance on the effectiveness of the programme. DESIGN: Follow up of non-attenders by practice nurses, including home visits if necessary, to administer questionnaires and obtain physiological measurements. SETTING: Eight general practices across England, Scotland, and Wales. SUBJECTS: Non-attenders in a cardiovascular risk factor screening and intervention programme compared with attenders. MAIN OUTCOME MEASURES: Number of non-attenders enrolled; sociodemographic characteristics; personal and family history of coronary heart disease; cardiovascular risk factors; and total coronary risk score. RESULTS: Data were collected from 106 (17%) of the 608 non-attending families (99 men and 42 women). Of the 543 non-attending families from five practices that attempted complete follow up, 256 had moved away or died. Only 76 were eventually enrolled into the study. The prevalence of coronary heart disease and a family history of coronary heart disease were similar among non-attenders and attenders as were the individual coronary risk factors studied except smoking. Women non-attenders were more likely to be current cigarette smokers than attenders (15/42 v 202/948, P = 0.02). CONCLUSIONS: The intensive follow up of non-attenders resulted in real intervention opportunities in only a small number. Since the effect of any intervention in a population is reduced by non-attendance audit of preventive medical programmes aimed at the population should allow for the effect of non-attenders on the overall results.

Cardiovascular Diseases↗